The role of glia and the cerebral vasculature in dementia

Dementia shrinks the brain's blood supply years before memory fails, and this project will test whether fixing that constriction can slow the disease. The problem is that current dementia treatments focus almost entirely on neurons, yet two other cell types—the blood vessels that feed the brain and the glial cells that support it—show damage long before symptoms appear. The researchers have already shown that a toxic protein called amyloid beta directly squeezes brain capillaries shut, starving neurons of oxygen. They have also found that immune cells called microglia can both clear that toxic protein and, in a harmful twist, also eat away healthy synapses. This project will work out the exact molecular mechanisms behind these processes. If successful, the work could open up entirely new classes of dementia drugs that target blood vessels and glial cells rather than neurons. That matters because every existing Alzheimer's drug has failed to stop the disease's progression. The researchers will also test whether restoring blood flow can prevent damage to the myelin sheaths that insulate nerve fibres, which would preserve the brain's communication speed. This is fundamental science with a clear therapeutic direction—understanding the basic biology of how capillaries constrict and how glia decide what to eat could reveal drug targets that no one has yet exploited.